Gary G. Anderson

Prevention of amputation by diabetic education

This prospective randomized study evaluated the influence of a simple education program on the incidence of lower extremity amputation in diabetic patients. Two hundred three patients were randomized into two groups: Group 1, education (103 patients, 203 limbs) and Group 2, no education (100 patients, 193 limbs). There were no significant differences in medical management or clinical risk factors between the two groups. The amputation rate was three times higher in Group 2 (21 of 177 limbs versus 7 of 177 limbs; p less than or equal to 0.025), the ulceration rate was three times higher in Group 2 (26 of 177 limbs versus 8 of 177 limbs; p less than or equal to 0.005), and there was no difference in the overall incidence of infection (2 of 177 limbs). Overall success in Group 1 was highly significantly different from Group 2 (160 of 177 limbs versus 128 of 177 limbs; p less than or equal to 0.0005). This study demonstrated that a simple education program significantly reduced the incidence of ulcer or foot and limb amputation in diabetic patients.

Prospective comparison of noninvasive techniques for amputation level selection

This study prospectively compared the following tests for their accuracy in amputation level selection: transcutaneous oxygen, transcutaneous carbon dioxide, transcutaneous oxygen-to-transcutaneous carbon dioxide, foot-to-chest transcutaneous oxygen, intradermal xenon-133, ankle-brachial index, and absolute popliteal artery Doppler systolic pressure. All metabolic parameters had a high degree of statistical accuracy in predicting amputation healing whereas none of the other tests had statistical reliability. Amputation site healing was not affected by the presence of diabetes mellitus nor were the test results for any of the metabolic parameters.

Results of Hyperbaric Oxygen Therapy during Temporary Middle Cerebral Artery Occlusion in Unanesthetized Cats

We evaluated the effect of hyperbaric oxygen (HBO) therapy on neurological function and infarct size in 33 unanesthetized cats subjected to temporary 6-hour or 24-hour occlusion of the middle cerebral artery (MCA) 7 to 10 days after transorbital implantation of a vessel occluder. HBO therapy (100% oxygen at 1.5 atmospheres absolute) was administered for 40 minutes during or after 6-hour occlusions and before, during, and after 24-hour occlusions. Neurological function was graded on a scale of 0 to 10 every 30 minutes before, during, and after occlusion and HBO treatments until it stabilized and then daily until the cats were killed 10 days after occlusion. The results were compared with observations in 13 untreated controls and 6 cats that received 100% O2 at atmospheric pressure during a 6-hour MCA occlusion. HBO therapy during the 1st or 3rd hour of a 6-hour MCA occlusion resulted in a four-grade improvement of the initial neurological function; this effect persisted during the remainder of the occlusion. The average grade of neurological deficit at death was 94% less than in the untreated cats (P less than 0.03). Infarct size in the HBO-treated group was 58% less than in controls (P less than 0.03). There was no significant difference in infarct size between the untreated cats and those treated with 100% O2 at atmospheric pressure. HBO therapy during the 4th hour of a 6-hour MCA occlusion had no statistically significant effect on infarct size, even though the mean neurological deficit was 73% less than in controls (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Fate of Insulin-Like Growth Factors I and II Administered Orogastrically to Suckling Rats

ABSTRACT: Milk-borne insulin-like growth factors I and II (IGF-I and -II) may be of importance in the differentiation of the gastrointestinal tract of the suckling. To test this hypothesis, 10- to 11-d-old suckling rats were given via an orogastric tube 125I-IGF-I (n = 6) or 125I-IGF-II (n = 6) in rat milk and killed 30 min later. The results of this study demonstrated that approximately 40% of the radioactivity administered was detected in the gastrointestinal tract for both 125I-IGF-I and 125I-IGF-II experiments. Gel chromatography of acid extracts of homogenates of gastrointestinal tissues and luminal contents demonstrated that a significant fraction of recovered radioactivity eluted in a position identical to “native” IGF. These findings were confirmed by subjecting similarly treated samples to high performance liquid chromatography. In addition, radioactive material recovered from Mr 7,500 fractions bound specifically to crude membrane IGF-I and -II receptor preparations, further suggesting the preservation of biologic activity of the recovered peptides. Although skin homogenates contained large peptide fragments of 125I-IGF-I, no “intact” IGF was found in the blood or other tissues. These findings suggest that milk-borne IGFs are stable in the neonatal gastrointestinal tract and remain biologically active for as long as 30 min postingestion.

Transcutaneous oxygen and carbon dioxide pressure monitoring to determine severity of limb ischemia and to predict surgical outcome

Transcutaneous oxygen and carbon dioxide pressure (PO2 and PCO2) foot monitoring was compared with ankle Doppler-derived systolic pressure regarding their respective abilities to discriminate the severity of limb ischemia before vascular reconstruction and to predict surgical outcome early in the postoperative period. Transcutaneous PO2 (tcPCO2), foot-chest tcPO2 index, transcutaneous PCO2 (tcPCO2), foot tcPO2/tcPCO2 index (tcPO2/tcPCO2), ankle Doppler systolic pressure (AP), and ankle-brachial pressure index (ABI) were determined in 89 revascularized limbs. The measurement of tcPO2 and foot-chest tcPO2 was found to be more sensitive to degrees of severity of limb ischemia and more closely associated with the outcome of revascularization than AP and ABI. TcPCO2 and tcPO2/tcPCO2 were not useful in assessment of the vascular patient undergoing reconstructive surgery. Before operation, tcPO2 less than or equal to 22 torr and foot-chest tcPO2 less than or equal to 0.46 indicate severe limb ischemia requiring urgent revascularization. After operation, tcPO2 less than or equal to 22 torr and foot-chest tcPO2 index less than or equal to 0.53 indicate that revascularization is likely to fail. We conclude that tcPO2 monitoring, as a metabolic test of actual tissue perfusion, is a more reliable indicator of preoperative limb ischemia and postoperative outcome of revascularization than hemodynamic, Doppler-derived pressure tests.

Effect of hyperbaric oxygen therapy or dimethyl sulfoxide on cerebral ischemia in unanesthetized gerbils.

To determine whether treatment with hyperbaric oxygen (HBO) or dimethyl sulfoxide (DMSO) could mitigate the fatal effects of cerebral ischemia, we anesthetized 68 gerbils with ketamine, ligated the right carotid artery (CA), and placed a snare occluder around the left CA. After 48 hours, 30 gerbils that were neurologically normal or had suffered only mild deficits were subjected to left CA occlusion without anesthesia for periods of 2 to 60 minutes. The onset of circling, posturing, falling, and lethargy began immediately; seizures and coma ensued 4 to 5 minutes later and persisted until release of the left CA occluder. All gerbils recovered after 2-minute staged bilateral CA occlusions. The mortality rate was 33% after both 5- and 10-minute occlusions and 100% after 20- and 60-minute bilateral occlusions. Twelve gerbils were placed in an HBO chamber (100% oxygen at 1.5 atmospheres) for 15 minutes during 20-minute bilateral occlusion; only 2 died (16% mortality rate). Thus, HBO therapy conferred significant protection against death from untreated ischemia (P less than 0.001). Histological examination showed that the extent of patchy bilateral ischemic neuronal damage was much less in surviving gerbils that received HBO therapy than in those that died after 20-minute occlusions. Fourteen gerbils were treated with DMSO, 2.5 g/kg intraperitoneally, during 5- or 10-minute bilateral CA occlusion; 12 died (86% mortality rate). Thus, DMSO provided no protection against fatal cerebral infarction; in fact, the results in the 10-minute reperfusion group suggest that DMSO may have a deleterious effect.

Distribution of disulfiram in brain after carotid ligation in gerbils

Aiming whether intraperitoneal administration of disulfiram (tetraethyl thiuram disulfide, DS) achieves potentially therapeutic drug concentrations in brain tissue, the behaviour of blood-brain barrier (BBB) to 14C-labelled DS in cerebral ischemia with and without simultaneous administration of dimethylsulfoxide (DMSO) was studied in Mongolian gerbils subjected to left common carotid artery (CCA) occlusion. The results indicated that: (a) the permeability of DS through the BBB was significantly enhanced in the ischemic brain during the initial 30 min duration after DS administration; (b) administration of DMSO increased the entry of DS into the ischemic brain five-fold during the first 30 min and it was significantly higher even at the 60 min sampling period; (3) in general, the content of DS in the brain was quickly reduced with time.

Secretion of Insulin-Like Growth Factor-II into Bile of Rats of Different Ages

Bile from rats of different ages (suckling 10–12 days; weanling 30–33 days, and adult 60–70 days) was collected and studied for the presence of immuno- and receptor-assayable insulin-like growth factor-II (IGF-II) concentrations. Concentrations of RIA IGF-II in bile were highest in suckling rats (230 ± 38 ng/ml) and lowest in adults (47 ± 7 ng/ml). These concentrations were approximately twice those of the bile IGF-I concentration in sucklings, as measured in a previous study. Selected bile samples were also assayed using a competitive binding assay with a crude preparation of adult rat liver membranes bearing the IGF-II receptor. These studies confirmed the presence of receptor- (as well as immuno-) active IGF-II in bile. Since bile flow rates increased dramatically after the suckling period, bile delivery rates of IGF-II were normalized as picograms per gram body weight per hour. When such calculations were done, bile IGF-II delivery rates to the small intestine were highest in sucklings and weanlings in comparison to adult rats. Thus non-enterically derived (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be approximated at roughly 1 μg/day. Unlike IGF-I, intravenously injected IGF-II could not be detected in suckling bile, suggesting a predominantly hepatic origin. From this study we conclude that there exists a significant delivery of receptor-active IGF-II to the gastrointestinal tract of rats of all ages.

EXCRETION OF INSULIN-LIKE GROWTH FACTOR-II (IGF-II) INTO BILE OF RATS OF VARYING AGES † 1883

EXCRETION OF INSULIN-LIKE GROWTH FACTOR-II (IGF-II) INTO BILE OF RATS OF VARYING AGES † 1883